tbuckley/cabot-search huggingface dataset:
The Anisotropic Component of the Diffusion Tensor (DTI-Q) Is Correlated to Overall Survival in Glioblastoma (GBM)
Authors: Natalie Simon, Rohit Sinha, Sanskrithi Sravanam, Roxanne Mayrand, Chao Li, Yizhou Wan, Yiran Wei, Stephen Price
Journal: Neuro-Oncology (2022)

Abstract AIMS The aim of this study was to test if a correlation exists between the median voxel DTI-Q and overall survival in patients with GBM. METHOD The median voxel anisotropic (DTI-Q) values, calculated for the whole brain, the contrast-enhancing hemisphere and the contralateral hemisphere, were calculated using FSL (FMRIB Software Library, Oxford) for 33 patients with a primary diagnosis of GBM. Overall survival was calculated by subtracting the date of initial resection surgery from the date of death, for each included patient. Using R statistical software, the Pearson’s correlation coefficient was computed to establish the significance of the relationship between overall survival and whole brain median DTI-Q values, contrast-enhancing hemisphere median DTI-Q values and non-contrast-enhancing hemisphere median DTI-Q values. RESULTS There is a significant correlation between the median voxel DTI-Q of the whole brain and overall survival (t = -2.5362, df = 31, p-value = 0.01646), median voxel DTI-Q of the contrast-enhancing hemisphere and overall survival (t = -2.1235, df = 31, p-value = 0.0418) and the median voxel DTI-Q of the contralateral (non-contrast-enhancing) hemisphere and overall survival (t = -2.5212, df = 31, p-value = 0.01705). CONCLUSION The median anisotropic component of the diffusion tensor, calculated for the whole brain, contrast-enhancing and non-contrast-enhancing hemisphere, is significantly related to overall survival. This demonstrates the potential utility of DTI metrics as prognostic biomarkers that can readily be calculated in routine practice.
How Can Clinical Teams Support Patients With a Brain Tumour Diagnosis With Sex Relationships and Intimacy?
Authors: Ellie Kostick, Jessica La, Victoria Hurwitz, Sarah Hedges, Charlotte Robinson, Aeron Suarez, Keyoumars Ashkan, Ranjeev Bhangoo, Richard Gullan, Francesco Vergani, Lucy Brazil, Omar Al-Salihi, Angela Swampillai, Kazumi Chia, Katia Cikurel, Dorothy Joe, Gerald Finnerty, Jose Pedro Lavrador
Journal: Neuro-Oncology (2022)

Abstract AIMS There is a gap in supporting patients with sexual relationships and intimacy. The aim of this study is to establish if patients with a brain tumour feel they are able to ask questions and concerns about sex, relationships and intimacy following diagnosis; is there an unmet need and how can this be addressed. METHOD An anonymous survey was sent to patients known to a neuro-oncology team. Questions were in relation to their experiences of sex relationships and intimacy. Patients were asked if they had concerns about changes in their relationships since their diagnosis. They were also asked for their comments on the subject so we can better understand how as a service we can improve to ensure holistic care. RESULTS There are 40 responses. The majority of respondents had concerns about their relationship since diagnosis and that their relationships have changed. 57% were concerned about a physical relationship with a partner/ future partners. 50% agreed their physical relationship had changed. 45% of people agreeing their emotional relationships have changed. 38 out of the 40 people questioned, had not asked their clinical team for advice about sex and relationships. 46% suggested clinicians initiating these conversations. CONCLUSION Sex relationships and intimacy are significant for most adult populations, encompassing connection with their loved ones, self esteem and psychological and emotional well-being. With brain tumour diagnosis this part of people’s lives can hugely impacted. Historically clinicians have found this a difficult subject to discuss. Further work is required to understand the barriers initiating this subject
10-Year Institutional Retrospective Case Series of WHO Grade II Gliomas and Correlation of Incidence of Seizures, Isocitrate Dehydrogenase No. 1 (IDH-1) Mutation and Lobar Location (2010-2020)
Authors: Simon Lammy, Elsie Bridgman, Hannah Johnson, Aaron Taylor, Athanasios Grivas
Journal: Neuro-Oncology (2022)

Abstract AIMS OBJECTIVES To assess the correlation in World Health Organisation (WHO) Grade II gliomas of IDH-1 mutation, lobar location and seizures DESIGN 10-year retrospective case series SUBJECTS Histopathological WHO Grade II gliomas METHODS We searched case notes in NHS Greater Glasgow &amp; Clyde and Scottish National PACS. RESULTS 84 patients underwent tissue diagnosis. Mean age 42rs (range: 21-77yrs]). Seizures (NB: pre-2017 International League against Epilepsy classification [ILAE]) occurred in 71% (52% generalised, 37% partial and 11% mixed). 31% had ongoing seizures postoperatively. 38% had headache (50% had headache and seizures). 21% had a focal neurological deficit (FND) (61% had a FND and seizure). Seizure, as an isolated pre-operative symptom occurred in 48% patients compared to isolated headache in 10% and isolated FND in 4%. Overall, 58% of lesions and 60% of seizures were frontal. Histologically, 60% were astrocytomas and 40% oligodendrogliomas (49% of astrocytomas and 71% of oligodendrogliomas arose from the frontal lobe). IDH-1 mutation occurred in 80% (75% had seizures) and 66% were frontal. CONCLUSION This confirms a correlation between IDH-1, incidence of seizures and frontal lesions (p = &amp;lt;0.05) REFERENCES Zhong et al. IDH1/2 Mutation is Associated with Seizure as an Initial Symptom in Low-Grade Glioma. Epilepsy Res. 2015 109:100-105
Rapid Early Progression (REP) of Glioblastoma Is an Independent Negative Prognostic Factor: Results From a Systematic Review and Meta-Analysis
Authors: Mueez Waqar, Federico Roncaroli, Eric Lehrer, Joshua Palmer, Javier Villanueva-meyer, Steve Braunstein, Emma Hall, Marianne Aznar, Philip Witt De Hamer, Pietro D’Urso, Daniel Trifiletti, Alfredo Quiñones-Hinojosa, Pieter Wesseling, Gerben Borst
Journal: Neuro-Oncology (2022)

Abstract AIMS In patients with newly-diagnosed glioblastoma, rapid early progression (REP) refers to tumour regrowth between surgery and postoperative chemoradiotherapy. This systematic review and meta-analysis aimed to appraise published data on REP to better characterise and understand this phenomenon. METHOD Systematic searches of MEDLINE, EMBASE and the Cochrane database from inception to 21/10/21. Studies describing the incidence of REP – tumour growth between the postoperative MRI scan and pre-radiotherapy MRI scan in newly-diagnosed glioblastoma, were included. The primary outcome was REP incidence. RESULTS From 1590 search results, 9 studies were included with 716 patients. The median age was 56.9 years (IQR 54.0- 58.8 years). There was a male predominance with a median male-to-female ratio of 1.4 (IQR 1.1-1.5). The median number of days between MRI scans was 34 days (IQR 18-45 days). The mean incidence rate of REP was 45.9% (range 19.3%-72.0%) and significantly lower in studies employing functional imaging to define REP (p&amp;lt;0.001). REP/non-REP groups were comparable with respect to age (p=0.99), gender (p=0.33) and time between scans (p=0.81). REP was associated with shortened overall survival (HR 1.78, 95% CI 1.30-2.43, p&amp;lt;0.001), shortened progression-free survival (HR 1.78, 95% CI 1.30-2.43, p&amp;lt;0.001), subtotal resection (OR 6.96, 95% CI 4-51-10.73, p&amp;lt;0.001) and IDH wildtype versus mutant tumours (OR 0.20, 95% CI 0.02-0.38, p=0.03). MGMT promoter methylation was not associated with REP (OR 1.29, 95% CI 0.72-2.28, p=0.39). CONCLUSION REP occurs in almost half of patients with newly-diagnosed glioblastoma and has a strongly negative prognostic effect. Future studies should investigate its biology and effective treatment strategies.
Predictors of Improved Outcomes in the Management of Newly Diagnosed Glioblastoma Multiforme – Retrospective Review of a Single Centre Experience
Authors: Charlotte Ziff, Louise Price, Abdelfattah Elmasry, Selvaraj Giridharan
Journal: Neuro-Oncology (2022)

Abstract AIMS To assess the benefit of combining maximal resection, Gliadel wafer insertion, CCRT and 4 or more cycles of adjuvant TMZ. METHOD We retrospectively reviewed a cohort of 110 patients who had undergone neurosurgery followed by chemo-radiotherapy (CRT) 60 Gray in 30 fractions and had at least one cycle of adjuvant TMZ from 2007 to 2016. Minimum follow up period 5 years. RESULTS Patients who had maximal safe debulking plus Gliadel wafer insertion, median OS was 19.5 months (95% confidence interval 14-30) those without wafers median OS was 16 months (95% confidence interval 14 – 21), P=0.06; significant on cox regression modelling. (P-value 0.008). Those continuing to receive at least 4 cycles of adjuvant TMZ median OS improved by 10 months compared to those unable to complete 4 cycles (10 vs 20 months). On cox analysis the number of adjuvant cycles of TMZ significantly affects OS, P-value 0.0003. Of these significant predictors of OS when combined (n=12) median OS was 18 months. Compared to 16 months for those who did not receive Glidel wafers and could not complete 4 cycles of TMZ following CRT. OS log-rank test P-value 0.4 CONCLUSION We were not able to demonstrate a statistically significant improved OS for those undergoing wafer insertion and completing at least 4 cycles of TMZ. Data may be inconclusive due to the small numbers, we conclude standard of care should still remain maximal safe debulking followed by CCRT and TMZ.
Clinical Outcome of Glioblastoma Treated in North Wales Cancer Treatment Centre Between 2014 and 2018
Authors: Niladri Ghosal, Pauline Burford, Mehrine Showkat, Ehsaan Ullah Abbasi, Mazin Sirelkhatim, Ravi Kodavatiganti, Ann Hind, Win Soe
Journal: Neuro-Oncology (2022)

Abstract AIMS Glioblastoma (GBM) is the most common primary brain tumour in adults and has a very poor clinical outcome. An audit of the clinical outcomes of patients with glioblastoma at our centre was conducted and compare with the results reported nationally in the National Cancer Registration Service and Hospital Episode Statistics 2007– 2011.[1] ) as well as international standards. METHOD Patients with GBM in North Wales Cancer Treatment Centre from October 2014 to September 2018 were identified using Canisc databases. We censored 2 patients because of no further follow up due to transferred to other centres. Treatment and outcome data was retrospectively collected using electronic record systems and the case notes. RESULTS The total 117 patients with GBM were identified. The craniotomy and Debulking surgery was done in 67, Biopsy only in 29 and no surgery in 21 patients. Median OS of all patients was 9.2 months. The median OS in the patient group of under 70 years treated with Concurrent chemo-radiotherapy (60 Gy) followed by adjuvant chemotherapy was 16.9 months. Median OS of patients aged 70 years and above who had “radiotherapy” or “no radiotherapy” were 6.5 months versus 1.9 months respectively. CONCLUSION Our results are comparable to the national outcomes. We would be reporting further on the differential survivals of different age groups and with results of genetic biomarker stratifications.
5-Aminolevulinic Acid (5-ALA) Use at The Walton Centre NHS Foundation Trust (WCFT)
Authors: Ruth Bennett, Elizabeth Akinsanya
Journal: Neuro-Oncology (2022)

Abstract AIMS To audit the use of 5-ALA at WCFT to determine adherence to NICE guidance [NG99] and the Trust guideline. METHOD Data was retrospectively evaluated from 77 patients prescribed 5-ALA at WCFT Jan 2020 – Jan 2022. RESULTS Of the 77 patients, 61 (79%) patients had 5-ALA induced fluorescence documented intraoperatively which aided resection and 7 patients (9%) had no confirmed fluorescence. In patients with no fluorescence noted, the administration time to operation time was variable. The remaining 9 patients (12%) had no documentation on the presence or absence of fluorescence. Prior to surgery, 67 patients had an MDT outcome of likely high grade glioma. 66 patients had this confirmed with histology post-surgical resection. The remaining patients had various MDT diagnosis documented including oligoastrocytoma, oligodendroglioma and lesion. 87% of patients had the correct dose of 20mg/kg prescribed. 14 patients (18%) did not have liver function tests (LFT) checked during admission as per Trust policy. Of those checked, 29 patients (37%) had new derangement of LFT. CONCLUSION The use of 5-ALA has aided surgical resection, enabling greater resection in the majority of patients prescribed for at WCFT. It has been used in accordance with NICE for HGG resections in 87% of cases. Some improvement could be made in ensuring the correct dose is prescribed and the appropriate monitoring (LFT) is carried out post procedure. Theatre documentation could be improved so future audit can more easily identify extent of resection and extent of fluorescence.
Association of Chronic Pancreatitis Pain Features With Physical, Mental, and Social Health
Authors: Dhiraj Yadav, Robert L. Askew, Tonya Palermo, Liang Li, Dana K. Andersen, Minxing Chen, William E. Fisher, Evan L. Fogel, Christopher E. Forsmark, Phil A. Hart, Mohamed O. Othman, Stephen J. Pandol, Walter G. Park, Mark D. Topazian, Stephen K. Van Den Eeden, Santhi Swaroop Vege, Yunlong Yang, Jose Serrano, Darwin L. Conwell
Journal: Clinical Gastroenterology and Hepatology (2022)
Seizure Semiology Over Time in Adult Diffuse Glioma
Authors: Claire Carstairs, Anmol Pandey, Zachary Moulder, Monika Kosela, Jeremy Rees
Journal: Neuro-Oncology (2022)

Abstract AIMS Patients with gliomas often present with generalised seizures, but subsequently develop focal seizures on treatment. The occurrence of a single generalised seizure at onset precludes the return of a driving licence, even if a patient continues to have only focal aware seizures. We investigated seizure semiology over time, to determine how many patients with ongoing seizures may be safe to drive. METHOD We analysed clinical data of patients with histologically-confirmed IDH-mutant diffuse gliomas, diagnosed between 2004-2015. Seizures were classified as: 1 – focal / 2 - generalised; A – aware / B – unaware; M – motor / N – non-motor. Seizure type at diagnosis and last follow-up was recorded. RESULTS 189 patients were identified, of whom 140 presented with seizures (74%). 115 of these patients had a full data set. 59 (51%) presented with generalised seizures. 10% had only a single seizure at presentation, 55 % had further seizures then became seizure-free and 35% continued to have seizures at last follow-up. Of the 40 patients who continued to have seizures, 7 (17.5%) had 1AN, 16 (40%) had 1AM, 1 (2.5%) had 1BN and 5 (12.5%) had 1BM. 11 (27.5%) had generalised seizures. Of the 7 patients with 1AN seizures at last follow-up, 4 initially presented with a generalised seizure, 1 with 1AN, 1 with 1AM and 1 with 1BM. CONCLUSION Almost two thirds of patients became seizure-free and, of those that continued to have seizures, 57.5% developed only focal aware seizures. Current driving regulations may be unduly restrictive for patients with gliomas.
Diagnostic Evolution of Synchronous Arteriovenous Malformation &amp; Glioblastoma: A Case Report
Authors: Jillian Davis, Rob Goldspring, Ian Scott, Stuart Smith, Arpita Chattopadhyay
Journal: Neuro-Oncology (2022)

Abstract AIMS We present the clinical course, radiology and histopathology of a case with synchronous pathology and aim to highlight learning points and diagnostic pitfalls. METHOD Case Notes, Radiology and Pathology were reviewed. RESULTS A 25 year old female with learning difficulties presented acutely with collapse. Initial CT-imaging demonstrated a right peritrigonal parenchymal haematoma with intraventricular extension. CT-Angiography revealed small vessels around the haematoma but no definite underlying vascular abnormality. Whilst the standard MRI sequences appeared to confirm the CT findings, the patient was unable to tolerate the planned MR angiogram or post-contrast sequences. Three months later, Digital Subtraction Angiography (DSA) revealed an “unusual” arteriovenous malformation (AVM) at the site of the previous haematoma. Over the following two months, the patient represented twice with acute headaches. CT imaging each time demonstrated further re-bleeds, with increasing oedema. Consequently, another DSA was performed for attempted embolisation but striking differences in the appearance of the AVM were now evident. Stereotactic radiosurgery was scheduled, but a planning CT-scan six weeks later revealed, for the first time, appearances suggestive of an underlying high-grade neoplasm. A biopsy was performed which showed a Glioblastoma (CNS WHO, 2021; Grade 4) alongside an arteriovenous malformation with well-developed arterial and venous structures. Despite optimal ICU management post-operatively, the patient deteriorated and sustained irreversible brain damage from which she did not recover. CONCLUSION Synchronous Glioblastoma and AVM is rare and can cause diagnostic and surgical challenges. These difficulties and the proposed angiogenic effects of tumour factors, as underlying aetiological agents of these synchronous lesions, is discussed.
Retrospective Review of Carcinomatous Meningitis Management at a Tertiary Centre: Reflections on Current and Future Management
Authors: Simon Williams, Oliver Topping, Paul Sanghera, Ghaniah Hassan-Smith
Journal: Neuro-Oncology (2022)

Abstract AIMS Carcinomatous meningitis (CM) arises following metastatic deposition of neoplastic cells in the meninges triggering a complex series of pathological changes, typically representing a terminal complication of underlying malignancy. No uniform management strategy exists for CM patients, despite research highlighting numerous treatment modalities. We present a single centre retrospective study of CM patients managed over a ten year period, along with analysis of current and future treatment modalities for CM. METHOD Patient datasets were identified using diagnostic codes. Inclusion criteria were patients with malignant cells identified in CSF, or those with radiological features consistent with CM with a background of cancer and supporting clinical features. Data regarding patient symptomatology, management, and outcome were then gathered from electronic patient records. RESULTS Ten cases of carcinomatous meningitis were identified. The most common primary tumour site was breast (30%). The most common presenting symptoms were headache (70%), weakness (60%), vomiting (50%), and confusion (50%). Radiological evidence of CM in the form of leptomeningeal enhancement was noted in 60% of cases. Management of CM cases was variable – six patients underwent no further anti-cancer treatment, two patients underwent chemotherapy, and two patients were planned for radiotherapy. Median length of survival from time of CM diagnosis was 30 days (IQR 15 – 63). CONCLUSION CM patients have a poor prognosis, and significant variability exists in management. New therapeutic options are emerging, particularly in the field of targeted biologic therapies, and engagement with specialist oncology teams is recommended. Early palliative care support is essential in the management of CM patients.
Adebrelimab (SHR-1316) in Combination With Chemotherapy as Perioperative Treatment in Patients With Resectable Stage II to III NSCLCs: An Open-Label, Multicenter, Phase 1b Trial
Authors: Wanpu Yan, Wen-Zhao Zhong, Yan-Hui Liu, Qixun Chen, Wenqun Xing, Qin Zhang, Lunxu Liu, Di Ge, Keneng Chen, Fan Yang, Xiang Lin, Li Song, Wei Shi, Yi-Long Wu
Journal: Journal of Thoracic Oncology (2022)
SYNGN: A Novel Patient-Specific Drug-Matching Strategy in Glioblastoma
Authors: Silvia Marino
Journal: Neuro-Oncology (2022)

Abstract AIMS The alteration of the glioblastoma genome by epigenetic mechanisms that share functions with normal developmental processes, such as self-renewal and fate specification of neural stem cells (NSC), is a key piece of evidence that links brain cancer pathogenesis with dysregulated stem cell functions. A patient-specific comparison of glioblastoma cells with NSC, a putative cell of origin of at least a proportion of these tumours, is not feasible as patient-matched endogenous NSC are not surgically accessible and all epigenetic studies in glioblastoma have so far compared epigenetic changes of different tumours with each other or to comparators obtained from foetal brains or an unrelated donor. We reasoned that availability of matched GIC and NSC pairs would allow to identify crucial epigenetic differences on a patient-specific basis and would provide essential therapeutic contrast to define disease-and patient-intrinsic biomarkers of drug response that are less confounded by germline variation. METHOD We have harnessed state-of-the-art stem cell technologies and next-generation sequencing methods to compare the epigenetic and transcriptional profile of IDH-wildtype glioblastoma with that of patient-matched normal expanded potential stem cell-derived NSC (iNSC). RESULTS We demonstrate that integrated analysis of the transcriptome and DNA methylome of GIC/iNSC pairs identifies druggable target genes (PTGER4, ALDH3B1, NTRK2 and others) in a proportion of patients and we validate this patient-specific prediction of drug response at pre-clinical level in 3D synGLICO and in in vivo models. CONCLUSION We provide proof of principle that the SYNGN platform can identify patient-specific druggable targets in glioblastoma.
Multifocal and Multicentric Glioblastomas: A 10 Year Single Centre Experience
Authors: Helen Maye, Georgios Mavrovounis, Federico Roncaroli, Catherine McBain, Matthew Bailey, Pietro D’Urso, David Coope, John Leach, James Leggate, Tina Karabatsou
Journal: Neuro-Oncology (2022)

Abstract AIMS The aims of this study are to share our experience of a large series of multifocal/multicentric glioblastomas (mGBM) and analyse the clinical, histological/molecular and neuroimaging characteristics as well as the outcomes of the patients in order to inform and contribute to future patient care. METHOD We conducted a retrospective single centre study of all multifocal/multicentric glioblastomas treated at our institution over a 10 year period. Data was collected from electronic patient records including patient demographics, clinical presentation, diagnostic imaging, treatment plans and histopathology/molecular findings. Time to recurrence/progression and overall survival was assessed. RESULTS 1158 glioblastomas were treated surgically over this time period of which 121 multifocal/multicentric tumours were identified (10.4%). The median age at diagnosis was 63 years with a slight male predominance (54.5%). Half of all patients (61/121) presented with focal neurological deficits. 69% of patients underwent a craniotomy for diagnosis/debulking of the larger enhancing component of the tumour whilst 31% underwent only a biopsy. The median time to recurrence/progression was 154 days. Median length of survival was 269 days. Those who underwent craniotomy had significantly prolonged survival compared to biopsy alone 301 vs 198 days (p= 0.027) as did those who had a near total resection 401 vs 269 for subtotal resection (P=0.006) and those &amp;lt; 60 years (p=&amp;lt; 0.001). 88% of patients were IDH1 wildtype. Radiotherapy and chemotherapy confer a significant survival advantage when compared with no further treatment (p&amp;lt;0.001). CONCLUSION Near total resection of the larger enhancing component and post-operative chemo/radiotherapy can offer prolonged survival in patients with mGBM.